Abstract An exciting development in the innate immunity field is the discovery that macrophages enlist autophagy to protect their cytoplasm from infection. Nutrient deprivation has long been known to induce autophagy, but how infection rapidly triggers this alternate route to digestive lysosomes is poorly understood. Genetic data indicate that mice resist L. pneumophila infection by relying on NOD-like proteins to detect cytosolic flagellin and then to digest the microbes by autophagy or to commit a pro-inflammatory cell death known as pyroptosis. To determine how macrophages integrate autophagy and pyroptosis as barriers to microbial infection, we will exploit Legionella pneumophila as a genetic probe of the innate immune system.